Association of MMPs/TIMPs polymorphism with alcohol-induced osteonecrosis of femoral head in the Chinese Han population

Alcohol-induced osteonecrosis of the femoral head (alcohol-induced ONFH) makes up almost one-third of the total proportion of non-traumatic ONFH. Polymorphism of matrix metalloproteinase (MMP) or tissue inhibitors matrix metalloproteinase (TIMP) is related to bone metabolic disorders. This study aimed to explore whether MMPs/TIMPs polymorphisms influenced alcohol-induced ONFH risk in the Chinese Han population. We selected 300 patients and 308 controls, with 18 single nucleotide polymorphisms (SNPs) successfully genotyped, and evaluated the association using the chi-squared test, Fisher's exact test, t-test, and genetic model analyses. We found that rs4789936 on TIMP-2 (OR = 0.75; 95% CI = 0.58-0.96; P = 0.025) decreased alcohol-induced ONFH risk under the allele model. After adjusting for age and gender, rs4789936 was significant in the dominant (OR = 0.63; 95% CI = 0.43-0.93; P = 0.018), overdominant (OR = 0.66; 95% CI = 0.45-0.98; P = 0.038), and log-additive (OR = 0.72; 95% CI = 0.53-0.97; P = 0.033) model. Furthermore, rs2277698 was significant in the overdominant model (OR = 0.66; 95% CI = 0.44-1.00; P = 0.049), which indicated the two SNPs had a protective function in decreasing alcohol-induced ONFH risk. In conclusion, rs4789936 and rs2277698 on TIMP-2 significantly decreased alcohol-induced ONFH risk in the Chinese Han population. Our study attempts to offer an objective basis for alcohol-induced ONFH clinical prevention.